Glucokinase

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Federal government websites often end in. The site is secure. Glucose transport is by facilitated diffusion and is not rate limiting. Once inside, glucose is phosphorylated to glucosephosphate by GCK in a reaction that is dependent on glucose throughout the physiological range of concentrations, is irreversible, and not product inhibited. High glycerol phosphate shuttle, pyruvate dehydrogenase, and pyruvate carboxylase activities, combined with low pentose-P shunt, lactate dehydrogenase, plasma membrane monocarboxylate transport, and glycogen synthase activities constrain glucosephosphate to being metabolized through glycolysis.

Glucokinase

Official websites use. Share sensitive information only on official, secure websites. The GCK gene provides instructions for making a protein called glucokinase. This protein plays an important role in the breakdown of sugars particularly glucose in the body. Glucokinase is primarily found in the liver and in beta cells in the pancreas. Beta cells produce and release secrete the hormone insulin, which helps regulate blood glucose levels by controlling how much glucose is passed from the bloodstream into cells to be used as energy. Glucokinase acts as a sensor, recognizing when the level of glucose in the blood rises and helping stimulate the release of insulin from beta cells to control it. In the liver, glucokinase helps determine when excess glucose should be taken in and converted to glycogen, which is a major source of stored energy in the body. Mutations in the GCK gene cause maturity-onset diabetes of the young MODY , which is a group of conditions characterized by abnormally high blood glucose levels. This form of diabetes usually begins before age Affected individuals usually have mildly elevated blood glucose levels from birth, although they typically have no symptoms associated with the condition, and diabetes-related complications are extremely rare. The altered protein may be broken down, or the function may be impaired, reducing glucokinase activity in cells. As a result, beta cells are less able to detect changes in blood glucose and release insulin to control it, so blood glucose remains elevated. The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

A "minimal mathematical model" has been devised based on the above kinetic information to predict the beta cell glucose phosphorylation glucokinase BGPR of normal "wild type" glucokinase and the known mutations, glucokinase.

Glucokinase EC 2. Glucokinase occurs in cells in the liver and pancreas of humans and most other vertebrates. In each of these organs it plays an important role in the regulation of carbohydrate metabolism by acting as a glucose sensor, triggering shifts in metabolism or cell function in response to rising or falling levels of glucose, such as occur after a meal or when fasting. Mutations of the gene for this enzyme can cause unusual forms of diabetes or hypoglycemia. Glucokinase GK is a hexokinase isozyme , related homologously to at least three other hexokinases. However, glucokinase is coded by a separate gene and its distinctive kinetic properties allow it to serve a different set of functions.

Federal government websites often end in. The site is secure. Glucose transport is by facilitated diffusion and is not rate limiting. Once inside, glucose is phosphorylated to glucosephosphate by GCK in a reaction that is dependent on glucose throughout the physiological range of concentrations, is irreversible, and not product inhibited. High glycerol phosphate shuttle, pyruvate dehydrogenase, and pyruvate carboxylase activities, combined with low pentose-P shunt, lactate dehydrogenase, plasma membrane monocarboxylate transport, and glycogen synthase activities constrain glucosephosphate to being metabolized through glycolysis. Under these conditions, glycolysis produces mostly pyruvate and little lactate. Pyruvate either enters the citric acid cycle through pyruvate dehydrogenase or is carboxylated by pyruvate carboxylase. Reducing equivalents from glycolysis enter oxidative phosphorylation through both the glycerol phosphate shuttle and citric acid cycle. Specific roles of different cell types are determined by the diverse molecular mechanisms used to couple energy state to cell specific responses. Having a common glucose sensor couples complementary regulatory mechanisms into a tightly regulated and stable glucose homeostatic network.

Glucokinase

Federal government websites often end in. The site is secure. Glucose metabolism in humans is tightly controlled by the activity of glucokinase GCK. GCK is predominantly produced in the pancreas, where it catalyzes the rate-limiting step of insulin secretion, and in hepatocytes, where it participates in glycogen synthesis. A multitude of disease-causing mutations within the gck gene have been identified. Activating mutations manifest themselves in the clinic as congenital hyperinsulinism, while loss-of-function mutations produce several diabetic conditions. Indeed, pharmaceutical companies have shown great interest in developing GCK-associated treatments for diabetic patients. Due to its essential role in maintaining whole-body glucose homeostasis, GCK activity is extensively regulated at multiple levels.

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In addition, the reaction products themselves may activate or inhibit metabolism not directly related to that of the original metabolite. This class of transactivators bind to the "E box" sequence of genes for a number of regulatory enzymes. Scientific Reports. Diabetes 64 , — In order to answer the question whether glucokinase acts as a glucose sensor in glucose-regulated glucagon release, we performed three sets of experiments manipulating the activity or expression of alpha cell glucokinase. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Image preparation for publication was performed using FIJI Keywords: diabetes, metabolic regulation, glucose homeostasis, counter regulatory hormones, glucokinase. Basco et al. In the context of glucokinase function, these cell types are collectively referred to as neuroendocrine tissues, and they share some aspects of glucokinase regulation and function, especially the common neuroendocrine promoter. This Ox-Phos model has been shown to predict behavior consistent with experimental measurement over a wide range of conditions, including those during the rest-to-work Wilson, b and work-to-rest Wilson, transitions in skeletal muscle. Insulin acting via the sterol regulatory element binding protein -1c SREBP1c is thought to be the most important direct activator of glucokinase gene transcription in hepatocytes. Lamy, C. Cell Biol. Our hypothesis is that glucokinase GCK is the primary glucose sensor in mammals and the sensor responsible for regulation of glucose homeostasis as schematically represented in Figure 1.

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Alpha cells occur in pancreatic islets, mixed with beta and other cells. Therefore, the general glucokinase reaction is more accurately described as: [6]. Oxidative phosphorylation: unique regulatory mechanism and role in metabolic homeostasis. Diabetes 54 , — Biochemical and Biophysical Research Communications. Top expressed in. Beta-cell secretory products activate alpha-cell ATP-dependent potassium channels to inhibit glucagon release. GCK has also been implicated in glucose sensing in the anterior pituitary gland of rat and monkey Zelent et al. The use of pHluorins for optical measurements of presynaptic activity. Incubation of alpha cells with either 10 mM 2-Deoxy- d -glucose Fig. Differential regulation of glucokinase activity in pancreatic islets and liver of the rat. This is considered strong evidence that GCK is responsible for the observed glucose dependences. Portal : Biology. Fine structure of the human galactokinase GAL-1 gene. Basel: S.